Genetic Tests in Paediatrics: An Ethical Reflexion

A autora aborda a problemática da biotecnologia em Medicina, designadamente dos testes genéticos em Pediatria e das suas implicações individuais e sociais. Nesse sentido, fundamenta a necessidade ética e científica de reflectir o seu indiscutível interesse, numa perspectiva biológica, sem descurar os riscos inerentes. A Ciência deve servir o homem como um fim e à luz da discussão sobre as bases filosóficas subjacentes à prossecução do Conhecimento, a autora defende o direito a não saber numa perspectiva de Autonomia, Pri-vacidade e Confidencialidade, designadamente nas doenças de manifestação tardia, de que é exemplo a Doença de Huntington

ETHICAL CONSIDERATIONS REGARDING GENETIC DISCRIMINATION IN THE CASE OF HUNTINGTON’S DISEASE

Huntington’s is a genetic neurodegenerative disease with dominant autosomal transmission, and high penetrance. This transmission model represents a high recurrence risk (50%) in case of the descendants of affected individuals. This disease can have its debut during adulthood, 40-50 years old or, in case of its juvenile form, during childhood or adolescence. The disease evolves with dystonia, choric movements, rigidity and dementia. Genetic testing for HD mutation is performed through molecular techniques and is possible at any age, independent of whether the person is symptomatic or asymptomatic. The genetic testing allows the identification of those individuals who are carriers of mutations on certain genes, these mutations being the underlying cause for some genetic diseases. At the present moment there are 3 types of genetic testing: diagnostic, carrier and predictive. The predictive tests identify whether an individual is a carrier for a certain specific genetic mutation and whether the possibility exists for him to develop certain health issues later on. Being aware of the carrier status for a certain genetic mutation for Huntington’s represents an element with major impact on the individual and on their family and can lead to discrimination from the side of the insurance companies, employers as well as others

ETHICAL CONSIDERATIONS REGARDING GENETIC DISCRIMINATION IN THE CASE OF HUNTINGTON’S DISEASE

Huntington’s is a genetic neurodegenerative disease with dominant autosomal transmission, and high penetrance. This transmission model represents a high recurrence risk (50%) in case of the descendants of affected individuals. This disease can have its debut during adulthood, 40-50 years old or, in case of its juvenile form, during childhood or adolescence. The disease evolves with dystonia, choric movements, rigidity and dementia. Genetic testing for HD mutation is performed through molecular techniques and is possible at any age, independent of whether the person is symptomatic or asymptomatic. The genetic testing allows the identification of those individuals who are carriers of mutations on certain genes, these mutations being the underlying cause for some genetic diseases. At the present moment there are 3 types of genetic testing: diagnostic, carrier and predictive. The predictive tests identify whether an individual is a carrier for a certain specific genetic mutation and whether the possibility exists for him to develop certain health issues later on. Being aware of the carrier status for a certain genetic mutation for Huntington’s represents an element with major impact on the individual and on their family and can lead to discrimination from the side of the insurance companies, employers as well as others

Contribution of scaling up nutrition Academic Platforms to nutrition capacity strengthening in Africa: local efforts, continental prospects and challenges

Addressing contemporary nutrition problems often require application of knowledge from multiple disciplines. The scaling up nutrition (SUN) movement harnesses multiple sectors for effective global and in-country planning and implementation. Although the role of knowl- edge networks (academia and research institutions) is recognised, the how of engaging knowl- edge networks in the current SUN architecture is only now becoming apparent. For relevant sectors to play their roles effectively, observed capacity gaps, particularly in developing coun- try settings, need to be addressed. The present paper presents the work being undertaken by the Ghana SUN Academic Platform, a local knowledge network, towards strengthening nutrition capacity in Ghana. The Platform presently provides technical support, evidence and capacity towards scaling up effective nutrition interventions in Ghana and beyond. The data presented draws heavily on the observations and collective experiences of the authors in practice, com- plemented by a review of relevant literature. The ultimate goal of the AP is to build capacity of professionals from nutrition and cognate sectors (including planning, agriculture, health, economics, research and academia). This is an essential ingredient for effective and durable SUN efforts. The paper recognises that both disciplinary and interdisciplinary capacity is required for effective SUN efforts in Africa, and offers an approach that utilises cross-sector/inter-professional, peer-learning and experiential learning initiatives

Predictive testing of minors for Huntington's disease: The UK and Netherlands experiences

A consistent feature of predictive testing guidelines for Huntington's disease (HD) is the recommendation not to undertake predictive tests on those < 18 years. Exceptions are made but the extent of, and reasons for, deviation from the guidelines are unknown. The UK Huntington's Prediction Consortium has collected data annually on predictive tests undertaken from the 23 UK genetic centers. DNA analysis for HD in the Netherlands is centralized in the Laboratory for Diagnostic Genome Analysis in Leiden. In the UK, 60 tests were performed on minors between 1994 and 2015 representing 0.63% of the total number of tests performed. In the Netherlands, 23 tests were performed on minors between 1997 and 2016. The majority of the tests were performed on those aged 16 and 17 years for both countries (23% and 57% for the UK, and 26% and 57% for the Netherlands). Data on the reasons for testing were identified for 36 UK and 22 Netherlands cases and included: close to the age of 18 years, pregnancy, currently in local authority care and likely to have less support available after 18 years, person never having the capacity to consent and other miscellaneous reasons. This study documents the extent of HD testing of minors in the UK and the Netherlands and suggests that, in general, the recommendation is being followed. We provide some empirical evidence as to reasons why clinicians have departed from the recommendation. We do not advise changing the recommendation but suggest that testing of minors continues to be monitored

Znaczenie badania psychiatrycznego w predykcyjnych badaniach genetycznych w kierunku choroby Huntingtona

Background and purpose Huntington disease (HD) is an autosomal dominant hereditary neurodegenerative disease with multiplication of CAG triplet in the short arm of chromosome 4, manifested by motor symptoms, cognitive dysfunction progressing to dementia, and various types of neuropsychiatric disorders. The diagnosis of HD is confirmed by a genetic test, which may also be carried out presymptomatically. Material and methods We studied differences in psychiatric examination and psychometric measures among the 52 people at risk of HD, who were recommended to postpone or to continue in the predictive protocol. In addition to the psychiatric examination, we administered the Eysenck Personality Questionnaire (EPQ-A), the Symptom Checklist 90 (SCL-90), and quality of life questionnaire (MANSA). Results People at risk of HD with the recommended test postponement showed lower rate of neuroticism and EPQ-A lie score, higher values on the phobia and the so-called ‘positive symptom distress index’ in SCL-90 and lower quality of life than people at risk of HD with the recommendation to continue. Conclusions Our results indicate that the formalized testing does not bring significant information whereas the clinical psychiatrie examination remains the main decisive factor in the recommendation to perform a predictive genetic test. The motivation of applicants is considered as the most important factor in the decision-making proces.Wstęp i cel pracy Choroba Huntingtona (ChH) jest dziedziczoną autosomalnie dominująco chorobą zwyrodnieniową układu nerwowego ze zwiększoną liczbą powtórzeń trypletów CAG na krótkim ramieniu chromosomu 4. Manifestuje się zaburzeniami ruchowymi, zaburzeniami poznawczymi postępującymi do otępienia oraz rozmaitymi zaburzeniami neuropsychiatrycznymi. Rozpoznanie ChH jest potwierdzane badaniem genetycznym, które może być wykonywane również u osób przed wystąpieniem objawów klinicznych. Materiał i metody Autorzy oceniali różnice w zakresie wyników badania psychiatrycznego i miar psychometrycznych wśród 52 osób zagrożonych rozwojem ChH, u których zalecano kontynuowanie lub odroczenie postępowania zmierzającego do wykonania badania genetycznego. Oprócz badania stanu psychicznego stosowano Eysenck Personality Questionnaire (EPQ-A), Symptom Checklist 90 (SCL-90) oraz kwestionariusz oceniający jakość życia (MANSA). Wyniki Osoby zagrożone wystąpieniem ChH, u których zalecano odroczenie badania genetycznego, uzyskiwały mniejszą punktację w skali Neurotyzmu i Kłamstw EPQ-A, większą punktację w skali oceny fobii i tzw. dodatniego wskaźnika obciążenia objawami w SCL-90, a także miały gorszą jakość życia niż osoby zagrożone ChH, u których zalecano kontynuowanie procedury zmierzającej do wykonania badania genetycznego. Wnioski Uzyskane wyniki wskazują, że sformalizowana ocena nie dostarcza istotnych informacji, podczas gdy kliniczne badanie psychiatryczne pozostaje głównym czynnikiem decydującym o zalecaniu wykonania badania genetycznego. Najważniejszym czynnikiem w podejmowaniu decyzji jest motywacja osób zgłaszających się na badanie

Huntington's disease: a clinical review

Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring full-time care, and finally death. The most common cause of death is pneumonia, followed by suicide

Amyotrophic Lateral Sclerosis in a Patient with a Family History of Huntington Disease: Genetic Counseling Challenges

Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are generally considered to be distinct and easily differentiated neurologic conditions. However, there are case reports of the co‐occurrence of ALS with HD. We present a 57‐year‐old male with a clinical diagnosis of sporadic ALS in the context of a family history of HD. This case adds to the limited literature regarding individuals with a family history of HD who present with features of ALS. There were several genetic counseling challenges in counseling this patient including the diagnostic consideration of two fatal conditions, complex risk information, the personal and familial implications, and the patient’s inability to communicate verbally or through writing due to disease progression. DNA banking effectively preserved the right of our patient and his wife not to learn his HD genetic status during a stressful time of disease progression while providing the option for family members to learn this information in the future if desired. We present lessons learned and considerations for other clinical genetics professionals who are presented with similar challenging issues.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147074/1/jgc40725.pd

Genetic counseling and testing practices for late-onset neurodegenerative disease: a systematic review

ObjectiveTo understand contemporary genetic counseling and testing practices for late-onset neurodegenerative diseases (LONDs), and identify whether practices address the internationally accepted goals of genetic counseling: interpretation, counseling, education, and support.MethodsFour databases were systematically searched for articles published from 2009 to 2020. Peer-reviewed research articles in English that reported research and clinical genetic counseling and testing practices for LONDs were included. A narrative synthesis was conducted to describe different practices and map genetic counseling activities to the goals. Risk of bias was assessed using the Qualsyst tool. The protocol was registered with PROSPERO (CRD42019121421).ResultsSixty-one studies from 68 papers were included. Most papers focused on predictive testing (58/68) and Huntington's disease (41/68). There was variation between papers in study design, study population, outcomes, interventions, and settings. Although there were commonalities, novel and inconsistent genetic counseling practices were identified. Eighteen papers addressed all four goals of genetic counseling.ConclusionContemporary genetic counseling and testing practices for LONDs are varied and informed by regional differences and the presence of different health providers. A flexible, multidisciplinary, client- and family-centered care continues to emerge. As genetic testing becomes a routine part of care for patients (and their relatives), health providers must balance their limited time and resources with ensuring clients are safely and effectively counseled, and all four genetic counseling goals are addressed. Areas of further research include diagnostic and reproductive genetic counseling/testing practices, evaluations of novel approaches to care, and the role and use of different health providers in practice

Alzheimer’s Prevention Initiative Generation Program: Development of an APOE genetic counseling and disclosure process in the context of clinical trials

IntroductionAs the number of Alzheimer’s disease (AD) prevention studies grows, many individuals will need to learn their genetic and/or biomarker risk for the disease to determine trial eligibility. An alternative to traditional models of genetic counseling and disclosure is needed to provide comprehensive standardized counseling and disclosure of apolipoprotein E (APOE) results efficiently, safely, and effectively in the context of AD prevention trials.MethodsA multidisciplinary Genetic Testing, Counseling, and Disclosure Committee was established and charged with operationalizing the Alzheimer’s Prevention Initiative (API) Genetic Counseling and Disclosure Process for use in the API Generation Program trials. The objective was to provide consistent information to research participants before and during the APOE counseling and disclosure session using standardized educational and session materials.ResultsThe Genetic Testing, Counseling, and Disclosure Committee created a process consisting of eight components: requirements of APOE testing and reports, psychological readiness assessment, determination of AD risk estimates, guidance for identifying providers of disclosure, predisclosure education, APOE counseling and disclosure session materials, APOE counseling and disclosure session flow, and assessing APOE disclosure impact.DiscussionThe API Genetic Counseling and Disclosure Process provides a framework for largeâ scale disclosure of APOE genotype results to study participants and serves as a model for disclosure of biomarker results. The process provides education to participants about the meaning and implication(s) of their APOE results while also incorporating a comprehensive assessment of disclosure impact. Data assessing participant safety and psychological wellâ being before and after APOE disclosure are still being collected and will be presented in a future publication.Highlightsâ ¢Participants may need to learn their risk for Alzheimer’s disease to enroll in studies.â ¢Alternatives to traditional models of apolipoprotein E counseling and disclosure are needed.â ¢An alternative process was developed by the Alzheimer’s Prevention Initiative.â ¢This process has been implemented by the Alzheimer’s Prevention Initiative Generation Program.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153071/1/trc2jtrci201909013.pd